Adipose-Resident Group 1 Innate Lymphoid Cells Promote Obesity-Associated Insulin Resistance

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2016 Aug 7

PMID 27496734

Citations 160

Authors

Timothy E OSullivan

Moritz Rapp

Xiying Fan

Orr-El Weizman

Priya Bhardwaj

Nicholas M Adams

Thierry Walzer

Andrew J Dannenberg

Joseph C Sun

Affiliations

Soon will be listed here.

Abstract

Innate lymphoid cells (ILCs) function to protect epithelial barriers against pathogens and maintain tissue homeostasis in both barrier and non-barrier tissues. Here, utilizing Eomes reporter mice, we identify a subset of adipose group 1 ILC (ILC1) and demonstrate a role for these cells in metabolic disease. Adipose ILC1s were dependent on the transcription factors Nfil3 and T-bet but phenotypically and functionally distinct from adipose mature natural killer (NK) and immature NK cells. Analysis of parabiotic mice revealed that adipose ILC1s maintained long-term tissue residency. Diet-induced obesity drove early production of interleukin (IL)-12 in adipose tissue depots and led to the selective proliferation and accumulation of adipose-resident ILC1s in a manner dependent on the IL-12 receptor and STAT4. ILC1-derived interferon-γ was necessary and sufficient to drive proinflammatory macrophage polarization to promote obesity-associated insulin resistance. Thus, adipose-resident ILC1s contribute to obesity-related pathology in response to dysregulated local proinflammatory cytokine production.

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